PROJECT SUMMARY Aging is associated with substantial cognitive decline across many domains. One factor that may play a role is age-related changes in neural distinctiveness?the extent to which neural activation patterns evoked by different stimuli are different. Our research group and others have found that neural distinctiveness tends to decline with age, and that older adults who maintain more distinctive neural representations perform better on a range of cognitive tasks. Previous animal work has found that levels of GABA (the brain?s major inhibitory neurotransmitter) decline with age and that pharmacological manipulations of GABA cause changes in neural distinctiveness. Based on this work, we hypothesize that age-related changes in cortical inhibition contribute to age-related declines in neural distinctiveness, which in turn contribute to behavioral impairments. We propose to test this model in humans. Specifically, we propose to investigate whether individual differences in cortical inhibition and GABA concentration in visual and motor cortex are associated with individual differences in neural distinctiveness and cognitive performance. We will recruit a large sample of older and younger adults and will then use transcranial magnetic stimulation to measure cortical inhibition, Magnetic Resonance Spectroscopy to measure GABA levels, functional MRI to measure neural distinctiveness, and a battery of validated tasks to measure cognitive performance. We will then test whether cortical inhibition and GABA levels are reduced in older vs. younger adults (Aim 1). We will also test whether individual differences in neural distinctiveness are associated with individual differences in cortical inhibition/GABA concentration (Aim 2). Finally, we will test whether individual differences in neural distinctiveness, in GABA, and in cortical inhibition are associated with individual differences in behavior (Aim 3). The proposed studies offer the hope of shedding light on the underlying causes of age-related impairments. Such an understanding is the first step in designing interventions that could slow, or conceivably even prevent, the behavioral impairments associated with healthy aging.